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天然存在的TPE-CA维持肠道微生物群和胆汁酸稳态 肝脏-肠道轴的FXR信号调节

Naturally Occurring TPE-CA Maintains Gut Microbiota and Bile Acids Homeostasis FXR Signaling Modulation of the Liver-Gut Axis.

作者信息

Liu Linlin, Liu Zhenli, Li Hui, Cao Zhiwen, Li Wen, Song Zhiqian, Li Xiang, Lu Aiping, Lu Cheng, Liu Yuanyan

机构信息

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.

Institution of Basic Theory, China Academy of Chinese Medical Sciences, Beijing, China.

出版信息

Front Pharmacol. 2020 Feb 6;11:12. doi: 10.3389/fphar.2020.00012. eCollection 2020.

Abstract

Antibiotics-induced changes in intestinal flora (dysbiosis) may have various effects on the host. Dysbiosis is associated with numerous metabolites including bile acids, which are produced in the liver from cholesterol and metabolized in the gut by intestinal microbiota. Total phenolic extracts of L. (TPE-CA) are rich in dietary flavanones and their glycosyl derivatives, including flavones, flavonols, polymethoxyflavones and coumarins, which exert positive health effects on the microbiota. The aim of this study is to elucidate the interplays between the intestinal microbiota and bile acids metabolism attributed to antibiotics. Mice were exposed to broad-spectrum antibiotics, such as ampicillin, streptomycin and clindamycin, for 14 days. This exposure resulted in reduced bacterial diversity and richness, and destroyed intestinal permeability. The homeostasis of bile acids was also affected. Subsequent TPE-CA administration, counteracted most of the dysbiosis, and reshaped intestinal permeability, these effects occurred upregulation of zonula occludens 1 and occludin associated proteins and downregulation of serum endotoxin compared to the antibiotics group. TPE-CA maintained the homeostasis of bile acids modulation of the liver-gut axis related farnesoid X receptor (FXR)/fibroblast growth factor 15 (FGF15) pathway and FXR-targeted protein. Our findings indicated that TPE-CA exerted a protective effect on the restoration of intestinal microbiota composition, reshaped barrier integrity and maintained bile acid homeostasis the liver-gut axis with antibiotics-induced dysbiosis.

摘要

抗生素引起的肠道菌群变化(生态失调)可能对宿主产生多种影响。生态失调与多种代谢产物有关,包括胆汁酸,胆汁酸由肝脏中的胆固醇产生,并在肠道中由肠道微生物群代谢。罗伊氏乳杆菌的总酚提取物(TPE-CA)富含膳食黄烷酮及其糖基衍生物,包括黄酮、黄酮醇、多甲氧基黄酮和香豆素,它们对微生物群具有积极的健康影响。本研究的目的是阐明抗生素引起的肠道微生物群与胆汁酸代谢之间的相互作用。将小鼠暴露于广谱抗生素,如氨苄青霉素、链霉素和克林霉素,持续14天。这种暴露导致细菌多样性和丰富度降低,并破坏了肠道通透性。胆汁酸的稳态也受到影响。随后给予TPE-CA,抵消了大部分生态失调,并重塑了肠道通透性,与抗生素组相比,这些作用表现为紧密连接蛋白1和闭合蛋白相关蛋白的上调以及血清内毒素的下调。TPE-CA通过调节肝肠轴相关的法尼醇X受体(FXR)/成纤维细胞生长因子15(FGF15)途径和FXR靶向蛋白维持胆汁酸的稳态。我们的研究结果表明,TPE-CA对恢复肠道微生物群组成、重塑屏障完整性以及在抗生素诱导的生态失调情况下维持肝肠轴的胆汁酸稳态发挥了保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b78d/7015895/63406fe5158f/fphar-11-00012-g001.jpg

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